A small US study among men who have sex with men has added new information to the debate around the links between HIV transmission and viral load levels in semen. The study, published in the August 20th issue of AIDS, found that blood viral load correlated better with transmission than seminal viral load. The study also investigated the role of infection with herpes simplex virus-2, finding an increased risk of HIV transmission, but only when the HIV source partner carried the virus.
Sexual transmission of HIV is affected by virological, biological and behavioural factors, such as viral load, mucosal inflammation and type of sexual intercourse. The complex interactions between these factors and the ways in which they might be modified to reduce the risk of transmitting the virus have been the subject of much debate, but there are limited solid empirical data.
The debate over the impact of viral load on HIV transmission was brought into the open earlier this year when the Swiss Federal AIDS Commission released a statement arguing that under very specific conditions the risk of someone with an undetectable viral load transmitting HIV falls to the point of being negligible. Controversy continued during a special satellite session on the subject at the International AIDS Conference in Mexico City and a conference late-breaker presentation of a meta-analysis of current data which demonstrated that it was impossible either to confirm or disprove the statements of the Swiss Federal AIDS Commission . These sessions suggest that for now, the debate involves politics and strong opinions, rather than just science.
The Swiss statement delivers a powerful message about HIV, but there are limitations of the evidence supporting the statement. (For an in-depth analysis of the statement, read the feature article in the April 2008 issue of HIV Treatment Update).
Among these limitations is the caveat that the statement applies only to vaginal intercourse; it does not address sex between men, a significant mode of transmission in many regions of the world, or anal intercourse between men and women.
Sexually transmitted infections (STIs) such as herpes simplex virus-2 (HSV-2) are known to increase the risk of HIV infection. However studies involving HSV-2 treatment have shown little effect in decreasing the risk of acquiring HIV, and so questions surrounding the role of HSV-2 in HIV transmission remain.
It is amid this uncertainty that investigators at the University of California, San Diego established a case-controlled study of men who have sex with men (MSM) to assess the impact of two factors on HIV transmission: viral load (in blood and in semen) and HSV-2 infection.
Investigators identified 47 pairs of men in which one partner was HIV-positive and there had been the potential for transmission through sexual exposure. Blood and semen samples were collected from the HIV-positive partner and the time between exposure and sample was estimated. Exposure date was identified as either the known date of sexual intercourse or as 14 days prior to screening, based on participants being told to recruit sexual partners from only the previous two weeks. The presence of HSV-2 was tested, and treatment with aciclovir or valaciclovir was noted. Both partners were also tested and treated for the bacterial sexually transmitted infections gonorrhoea, chlamydia and syphilis.
Transmission of HIV was documented in 15 couples by phylogenetic analysis (comparison of genetic sequences in order to establish whether the partner had been infected by the HIV-positive study participant). Only one of the source partners was taking antiretroviral therapy at the time transmission was estimated to have occurred, and that person was found to have a detectable viral load in blood. There was no transmission in the remaining 32 couples (five of the HIV-positive individuals in this group were taking antiretroviral therapy). The groups were then compared to identify factors associated with transmission.
Investigators evaluated the link between viral load in blood and semen, and transmission. Viral load samples were collected a median of 103 days after exposure was estimated to have taken place (range 20-146 days after) in the transmitter group and a median of 24 days after a potential exposure in the non-transmitter group (range 107 days before - 42 days after).
Median blood viral load was higher in the group in which transmission took place than in the non-transmitting group, though in both groups viral loads of over 10,000 copies/ml were recorded (55,000 copies/ml in the transmission group versus 11,700 copies/ml in the non-transmitters, p
Upon multivariate analysis, blood viral load was significantly associated with transmission; semen viral load was not. The range of blood viral loads among transmitters had a higher maximum and narrower range of values than the non-transmitting group. However, the range of semen viral loads for transmitters fell completely within the range of semen viral loads for non-transmitters.
The association in this study between sexual transmission and blood viral load, but not seminal viral load, was puzzling, given that sexual transmission involves seminal virus not blood-borne virus. The investigators hypothesise that “this may well be artifactual owing to the lag between sexual exposures and specimen collections.” The median estimated time between exposure and sample collection was significantly longer for the transmitting group than the non-transmitting group (103 days versus 24 days, p
The authors also note that their study measured cell-free virus in semen, not cell-associated virus. The authors note that the respective roles of cell-free and cell-associated virus in HIV transmission via semen have not been defined, and acknowledge that the measurement of cell-free virus may prove to be a limitation of the study.
When investigators turned their attention to HSV-2, they noted that HSV-2 infection was associated with transmission, but only when infection was present in the source partner. “These results,” the investigators write, “suggest that asymptomatic HSV-2 infection may have an impact on the risk of transmission rather than acquisition of HIV-1.”
While current studies into the treatment of herpes have shown little effect on reducing risk of HIV infection, the investigators suggest, “a role for suppressive therapy of asymptomatic HSV-2 infection may exist, but it may be indicated for HIV-infected people to reduce their risk of transmitting HIV-1 rather than for HIV-uninfected people to reduce their risk of acquiring HIV-1, as has been investigated to date. This must be determined empirically.”
Butler D.M. et al. Herpes simplex virus 2 serostatus and viral loads of HIV-1 in blood and semen as risk factors for HIV transmission among men who have sex with men. AIDS 22:1667 – 1671, 2008.